INSILICO (03696.HK): First-in-Human ISM6331 Data Show 40% ORR in 130mg Mesothelioma Cohort

NewTimeSpace News: On 27 October 2026, InSilico Medicine (stock code: 3696) announced that preliminary first-in-human Phase I data for ISM6331, an investigational oral pan-TEAD inhibitor designed with its generative AI platform Chemistry42, were presented as a rapid oral presentation at the 2026 ESMO Congress.

As at the data cut-off of 14 August 2026, the Phase I study (NCT06566079) had enrolled 36 subjects across 15 to 130 mg, with a median of two prior lines of therapy (range 1 to 12), and is in the dose-escalation phase. Among evaluable mesothelioma subjects, the 130 mg once-daily cohort achieved an objective response rate (ORR) of 40%; across 30 to 130 mg, the disease control rate (DCR) at the first tumour assessment was 68.2%, and the ORR in mesothelioma was 18.2% (four of 22), with responses observed in the 30 mg, 50 mg and 130 mg cohorts.

Three of the four responders achieved a response at the first assessment at week 8; as at the cut-off, three partial responses were ongoing, one of which had lasted nearly a year. Beyond mesothelioma, preliminary antitumour signals included target lesion shrinkage in heavily pretreated non-small cell lung cancer (seven prior lines) and head and neck squamous cell carcinoma (eight prior lines), and disease stabilisation lasting more than four months in epithelioid haemangioendothelioma and colorectal cancer.

No dose-limiting toxicities were reported across 15 to 130 mg and no treatment-related adverse events led to permanent discontinuation. Most adverse events were grade 1 or 2, with grade 3 events in only 8.3% of subjects, including asymptomatic amylase and lipase elevations, fatigue and drug dermatitis; treatment-related proteinuria occurred in 11.1% and was grade 1 or 2 and reversible. Circulating CCN2 levels were consistently downregulated, and a terminal half-life of about 18 to 32 hours supports once-daily dosing. ISM6331 received FDA orphan drug designation in 2024 and fast track designation in July 2026.